In recent years, there has been great emphasis on the promotion, enhancement, or at least maintenance of normal hair growth on the human head, particularly with men whose hair has started to recede, as in male pattern baldness, or with both men and women, as hair becomes thinner with advancing age. To this end, the market in "hair restorers" or "baldness cures" is growing.
There has also for many years existed a demand for products which are capable of removing unwanted hair, particularly from other parts of the body, such as the legs, armpits and face, without recourse to shaving. This demand has been greater for women than for men, although men would undoubtedly welcome a means for permanently or semi-permanently removing hair from the face, if only to avoid the daily need to shave.
The products that are currently available for topical use in the removal of unwanted hair are mostly based on thioglycollates as the active ingredient. Examples are those available under the trade names VEET and NAIR. Thioglycollates function in this role as reducing agents at high pH, by reducing disulphide bonds in hair, following penetration into the follicular canal, where the hair is weakened in the region above the keratinizing zone. The hair shaft can then break off just below the skin surface leaving a soft., smooth surface feel to the skin.
Hair growth does not however cease and, since the hair is broken near the skin surface, regrowth occurs within a relatively short time and the cosmetic advantage is thus rapidly lost. Retreatment with the thioglycollate product is then necessary, if the treated skin is to be maintained in a hairless condition.
There is consumer resistance to the use of thioglycollate hair removal product as skin irritation is sometimes encountered, but as no alternative methods of hair removal exist, apart from shaving and plucking of individual hairs, vanity demands that thioglycollate-containing products offer the most effective method, particularly for women, for the removal of unwanted hair from the body surface.
It is well established that in most mammals, including man, hair does; not grow continuously, but undergoes a cycle of activity involving alternate periods of growth and rest. The hair growth cycle can be divided into three main stages, namely:
i) an active stage known as anagen, during which the hair follicle penetrates deep into the dermis with the cells of the bulb dividing rapidly and differentiating to form the hair, PA1 ii) a regressive stage known as catagen, which is heralded by the cessation of mitosis, and during which the follicle regresses upwards through the dermis and hair growth ceases, and PA1 iii) a resting stage known as telogen, in which the regressed follicle contains a small secondary germ with an underlying ball of tightly packed dermal papilla cells. PA1 i) a two step treatment in which hair is first removed by a conventional method and then regrowth prevented, or retarded by subsequent application of the substance; or PA1 ii) a one step treatment in which the rate of hair growth is reduced, by application of the substance, without necessarily being accompanied by consequential hair loss, for example in beard growth. PA1 i) an effective amount of an inhibitor of glutamine metabolism in the hair follicle; and PA1 ii) a cosmetically acceptable vehicle for the inhibitor. PA1 R' is a polyether group having the structure: PA1 --CH.sub.3 H.sub.5 O(C.sub.2 H.sub.4 O).sub.a (CH.sub.3 C.sub.2 H.sub.3 O).sub.b R" PA1 a has a value of from 9 to 115, PA1 b has a value of from 0 to 50, PA1 x has a value of from 133 to 673, PA1 y has a value of from 25 to 0.25. PA1 a has a value of from 10 to 114 PA1 b has a value of from 0 to 49 PA1 x has a value of from 388 to 402 PA1 y has a value of from 15 to 0.75 PA1 a has the value 14 PA1 b has the value 13 PA1 x has the value 249 PA1 y has the value 1.25
The metabolism of the hair follicle during growth is not well understood. It has been established on microdissected hair follicles that glucose is a major fuel which the hair follicle requires for normal growth and that glucose is not oxidized to any great extent, as most of it is converted to lactate. [See, for example, Adachi K, Uno H. Glucose Metabolism of Growing and Resting Hair Follicles. Am J Physiol (1968) 215, 1234-1239; and Philpott M P, Kealey T, Metabolic Studies on Isolated Hair Follicles. J Invest Derm (1991) 96, 875-879].
In more recent work, we have shown that surprisingly, the hair follicle metabolises very little lipid fuels. Instead, glutamine has emerged as a major fuel which yields as much energy to the hair follicle as does glucose. We have also shown that glutamine is largely metabolized to lactate, and that the rate of hair growth in vitro will only match that seen in vivo if both glucose and glutamine fuels are present at the same time.
Armed with this new knowledge that glutamine is important to normal hair growth, we have now shown that in in vitro experiments, the use of certain inhibitors which prevent glutamine from being converted to lactate also interfere with hair growth. It follows, that by careful selection of an inhibitor of at least one of the steps in the glutamine-lactate metabolic pathway, particularly that concerned with converting glutamine to pyruvate, topical application of the inhibitor can reduce or retard hair growth, or even eliminate hair growth altogether.
The invention is accordingly concerned with the selection of one or more substances that will modulate mammalian hair growth by inhibiting at least one of the enzymes involved in glutamine metabolism.
It is furthermore envisaged that these substances can be employed in one of several treatments for eliminating unwanted hair from the body surface, or at least in reducing its rate of growth, such as:
The invention is accordingly also concerned with the use of inhibitors of glutamine metabolism in the hair follicle, in retarding or eliminating hair growth.